Interpretive Summary: Research has demonstrated that it is more effective to prevent adverse response to disease than to treat disease once it has set into a herd. The present study was aimed at increasing our understanding of why cattle implanted with a traditional growth promotant containing estradiol and - progesterone are better able to cope with disease stress than some nonimplanted cattle. We used an immune challenge based on the administration of a bacterial toxin to mimic a disease response of an animal without the need to actually infect the animal with anything. Our data suggested that some of the positive effects of the growth implant were associated with a decreased production of some nitrogen containing compounds that turn into tissue-destructive free radicals and some hormones that adversely affect blood flow in some organs. In addition, the data demonstrated that the duration of the fever that develops during the course of the host response to the toxin was shortened in comparison to the time over which nonimplanted calves presented clinical signs of fever. Overall, the use of selective implants to regulate too severe a reaction to a disease insult may benefit overall animal health and decrease production costs associated with poor food intake.

Technical Abstract:
Estradiol plus progesterone (EP) implants have been shown to delay the onset or reduce the severity of many of the clinical signs associated with coccidiosis and endotoxemia in calves. We explored a possible mechanism through which EP could exert these beneficial effects by systematically characterizing the effect of pretreatment with EP on the production of tumor necrosis factor-a (TNF), the vasoactive arachadonic acid metabolites thromboxane (TXB) and prostacyclin (PRC), plasma nitrite and nitrate (NOX), the stable end products of nitric oxide synthase (NOS)-driven arginine-derived nitric oxide (NO), and cortisol (CORT) as a measure of the glucocorticoid stress component. Holstein steer calves were divided into 4 groups: control, EP, endotoxin, and EP+endotoxin (n=5/group). EP pellets (Synovex-Sâ) were implanted when calves reached 4 mos. of age. One week after implant calves were injected with endotoxin (0.6 mg/kg BW) or nonpyrogenic saline placebo. Body temperature increased in both endotoxin and endotoxin-EP calves, but had returned to normal by 6 h in the endotoxin-EP group (P<0.05). Plasma TNF and CORT increased after endotoxin (P<0.01), but were not differentially affected by EP treatment. Likewise, EP did not affect the magnitude of increase in endotoxin-induced PRC but did reduce the magnitude of increase in TXB (P<0.05). Plasma NOX levels were elevated (P<0.01) in calves after endotoxin; treatment with EP attenuated the endotoxin-associated increase in plasma NOX levels. These data suggest that EP exerts specific effects on different components of the proinflammatory cytokine cascade. Components of the nitric oxide- and TXB-axis responses to endotoxin are decreased in calves pretreated with EP.